Within several decades, the area of inflammation and cancer has attracted great attention. During the process of tumor initiation and progression, a variety of inflammatory cytokines including interleukin-6 entangle tumor cells and the surrounding tumor microenvironment into an inflammatory net; STAT3 (signal transducers and activators of transcription 3) is the key player in the net that persistently promotes tumor development. This review begins with the composition of STAT3 signaling pathways, and discusses its role in different cell types regarding the network between tumor cells and tumor microenvironment, and its advance in translational research on targeted cancer therapy.